Measles (rubeola) is an acute viral infection caused by an RNA virus, characterized by a maculopapular rash and high fever, with significant contagiousness primarily through respiratory droplets. Effective vaccination has reduced incidence rates, but the disease remains serious, particularly in malnourished infants. The virus can cause various complications, including pneumonia and encephalitis, and requires supportive care, while vaccination, especially the MMR vaccine, is critical for prevention.

1. Measles (Rubeola) Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah ,UAE [email_address]

2. Measles (Rubeola) It is an acute viral infection characterized by a final stage with a maculopapular rash erupting successively over the neck and face, trunk, arms, and legs, and accompanied by a high fever.

3. Etiology Measles virus, the cause of measles, is an RNA virus of the genus Morbillivirus in the family Paramyxoviridae. Only one serotype is known

4. Epidemiology Measles is endemic throughout the world. In the past, epidemics tended to occur irregularly , appearing in the spring in large cities at 2-4-yr intervals as new groups of susceptible children were exposed.

5. Epidemiology (Cont.) It is rarely subclinical . Prior to the use of measles vaccine, the peak incidence was among children 5-10 yr of age.

6. Epidemiology (Cont.) Individuals born before 1957 are considered to have had natural infection and to be immune

7. TRANSMISSION Measles is highly contagious ; approximately 90% of susceptible household contacts acquire the disease. Maximal dissemination of virus occurs by droplet spray during the prodromal period ( catarrhal stage ).

8. TRANSMISSION (Cont.) Transmission to susceptible contacts often occurs prior to diagnosis of the index case Infants acquire immunity transplacentally from mothers who have had measles or measles immunization.

9. TRANSMISSION (Cont.) This immunity is usually complete for the first 4-6 mo of life and wanes at a variable rate. Some protection persists that may interfere with immunization administered before 12 mo of age .

10. TRANSMISSION (Cont.) Most women of childbearing age in the United States now have measles immunity by means of immunization rather than disease

11. TRANSMISSION (Cont.) infants of mothers with measles vaccine-induced immunity lose passive antibody at a younger age than infants of mothers who had measles infection .

12. TRANSMISSION (Cont.) Infants of mothers who are susceptible to measles have no measles immunity and may contract the disease simultaneously with the mother before or after delivery

13. Incidence and percentage of import-associated measles cases, by year – United States, 1985 to 2003 Centers for Disease Control and Prevention. Epidemiology of Measles – United States, 2001–2003. MMWR 2004;53:713–716.)

14. Number of measles cases, by import status and week of rash onset – United States, 2004 Centers for Disease Control and Prevention. Measles – United States. MMWR 2005;54:1229–1231

15. Number of confirmed measles cases and percentage of routine infant measles vaccination coverage – the Americas, 1980–2000. Centers for Disease Control and Prevention. Progress toward interrupting indigenous measles transmission – region of the Americas, January 1999–September 2000. MMWR 2000;40:986–990

16. Pathogenesis The essential lesion of measles is found in the skin , conjunctivae , and the mucous membranes of the nasopharynx , bronchi , and intestinal tract . Serous exudate and proliferation of mononuclear cells and a few polymorphonuclear cells occur around the capillaries .

17. Pathogenesis (cont.) Hyperplasia of lymphoid tissue usually occurs, particularly in the appendix, where multinucleated giant cells of up to 100 μm in diameter ( Warthin-Finkeldey reticuloendothelial giant cells ) may be found. In the skin , the reaction is particularly notable about the sebaceous glands and hair follicles.

18. Pathogenesis (cont.) Koplik spots consist of serous exudate and proliferation of endothelial cells similar to those in the skin lesions. A general inflammatory reaction of the buccal and pharyngeal mucosa extends into the lymphoid tissue and the tracheobronchial mucous membrane.

19. Pathogenesis (cont.) Interstitial pneumonitis resulting from measles virus takes the form of Hecht giant cell pneumonia . Bronchopneumonia may occur from secondary bacterial infection .

20. Pathogenesis (cont.) In fatal cases of encephalomyelitis , perivascular demyelinization occurs in areas of the brain and spinal cord. In subacute sclerosing panencephalitis (SSPE), there may be degeneration of the cortex and white matter with intranuclear and intracytoplasmic inclusion bodies

21. Measles has three clinical stages: 1. an incubation stage 2. a prodromal stage with an enanthem (Koplik spots) and mild symptoms 3. a final stage with a maculopapular rash accompanied by high fever. Clinical Manifestations

22. The incubation period lasts approximately 10-12 days to the first prodromal symptoms and another 2-4 days to the appearance of the rash; rarely, it may be as short as 6-10 days . Body temperature may increase slightly 9-10 days from the date of infection and then subside for 24 hr or so. The patient may transmit the virus by the 9th-10th day after exposure and occasionally as early as the 7th day, before the illness can be diagnosed

23. The prodromal phase usually lasts 3-5 days and is characterized by: * low-grade to moderate fever * dry cough * coryza * conjunctivitis . These symptoms nearly always precede the appearance of Koplik spots , the pathognomonic sign of measles, by 2-3 days .

24. The prodromal phase (cont.) The conjunctival inflammation and photophobia may suggest measles before Koplik spots appear. In particular, a transverse line of conjunctival inflammation , sharply demarcated along the eyelid margin, may be of diagnostic assistance in the prodromal stage . As the entire conjunctiva becomes involved, the line disappears.

25. Koplik spots An enanthem or red mottling is usually present on the hard and soft palates the pathognomonic sign of measles :

26. Koplik spots (cont.) are grayish white dots , usually as small as grains of sand, that have slight, reddish areolae ; occasionally they are hemorrhagic . tend to occur opposite the lower molars but may spread irregularly over the rest of the buccal mucosa.

27. Koplik spots (cont.) Rarely they are found within the midportion of the lower lip , on the palate , and on the lacrimal caruncle . They appear and disappear rapidly , usually within 12-18 hr . As they fade , a red , spotty discoloration of the mucosa may remain.

28. The prodromal phase (cont.) Occasionally , the prodromal phase may be severe , being ushered in by a sudden high fever , sometimes with convulsions and even pneumonia . Usually the coryza, fever, and cough are increasingly severe up to the time the rash has covered the body. The temperature rises abruptly as the rash appears and often reaches 40°C (104°F) or higher.

29. The prodromal phase (cont.) In uncomplicated cases , as the rash appears on the legs and feet, the symptoms subside rapidly within about 2 days , usually with an abrupt drop in temperature to normal. Patients up to this point may appear desperately ill, but within 24 hr after the temperature drops, they appear well .

30. The rash usually starts as faint macules on the: * upper lateral parts of the neck * behind the ears * along the hairline * posterior parts of the cheek .

31. The rash (cont.) The individual lesions become increasingly maculopapular as the rash spreads rapidly over the: * entire face * neck * upper arms * upper part of the chest within approximately the first 24 hr

32. Korting GW: Hautkrankheiten bei Kindern und Jugendlichen , 3rd ed. Stuttgart, FK Schattauer Verlag, 1982 Maculopapular rash of measles

33. The rash (cont.) During the succeeding 24 hr the rash spreads over the back, abdomen, entire arm, and thighs. As it finally reaches the feet on the 2nd-3rd day , it begins to fade on the face.

34. Typical rash on day 2–3 of measles (Courtesy of J.H. Brien.)

35. Rash on day 5 of measles showing typical confluence and density on head with scattered lesions on the trunk. (Courtesy of J.H. Brien.)

36. The rash (cont.) The rash fades downward in the same sequence in which it appeared. The severity of the disease is directly related to the extent and confluence of the rash. In mild measles the rash tends not to be confluent , and in very mild cases there are few, if any, lesions on the legs.

37. The rash (cont.) In severe cases the rash is confluent , the skin is completely covered, including the palms and soles, and the face is swollen and disfigured. The rash is often slightly hemorrhagic ; in severe cases with a confluent rash, petechiae may be present in large numbers, and there may be extensive ecchymoses

38. The rash (cont.) The appearance of the rash may vary markedly. Infrequently a slight urticarial , faint macular , or scarlatiniform rash may appear during the early prodromal stage, disappearing in advance of the typical rash.

39. The rash (cont.) Complete absence of rash is rare except : 1. in patients who have received immunoglobulin (Ig) during the incubation period 2. in some patients with HIV infection 3. occasionally in infants younger than 9 mo of age who have appreciable levels of maternal antibody.

40. The rash (cont.) In the hemorrhagic type of measles ( black measles ), bleeding may occur from the mouth, nose, or bowel. In mild cases the rash may be less macular and more nearly pinpoint , somewhat resembling that of scarlet fever or rubella

41. The rash (cont.) Itching is generally slight . As the rash fades , branny desquamation and brownish discoloration occur and then disappear within 7-10 days.

42. The prodromal phase (cont.) Otitis media bronchopneumonia gastrointestinal symptoms such as diarrhea and vomiting Are more common in infants and small children (especially if they are malnourished) than in older children.

43. Diagnosis The diagnosis is usually apparent from the characteristic clinical picture ; laboratory confirmation is rarely needed Testing for measles IgM antibodies is recommended in some situations Measles IgM is detectable for 1 mo after illness , but sensitivity of IgM assays may be limited in the first 72 hr of the rash illness.

44. Diagnosis (cont.) Isolation of measles virus from clinical samples is also useful in identifying the genotype of the strain to track transmission patterns. All suspected measles cases should be reported immediately to local or health departments. During the prodromal stage multinucleated giant cells can be demonstrated in smears of the nasal mucosa.

45. Diagnosis (cont.) Antibodies become detectable when the rash appears ; testing of acute and convalescent sera demonstrates the diagnostic seroconversion or fourfold increase in titer. Measles virus can be isolated by tissue culture in human embryonic or rhesus monkey kidney cells.

46. Diagnosis (cont.) Cytopathic changes , visible in 5-10 days, consist of multinucleated giant cells with intranuclear inclusions . The white blood cell count tends to be low with a relative lymphocytosis Cerebrospinal fluid in patients with measles encephalitis usually shows an increase in protein and a small increase in lymphocytes . The glucose level is normal.

47. The rash of rubeola must be differentiated from that of: Rubella Roseola infantum (human herpesvirus 6) Infections resulting from: * echovirus * coxsackievirus * adenovirus Infectious mononucleosis Toxoplasmosis Meningococcemia Scarlet fever Rickettsial diseases Kawasaki disease Serum sickness Drug rashes

48. Treatment There is no specific antiviral therapy; treatment is entirely supportive . Antipyretics (acetaminophen or ibuprofen) for fever bed rest maintenance of an adequate fluid intake are indicated.

49. Treatment (cont.) Humidification may alleviate symptoms of laryngitis or an excessively irritating cough; it is best to keep the room comfortably warm rather than cool. Patients with photophobia should be protected from exposure to strong light . Bacterial complications of otitis media and bronchopneumonia require appropriate antimicrobial therapy.

50. Treatment (cont.) Complications such as encephalitis, subacute sclerosing panencephalitis, giant cell pneumonia, and disseminated intravascular coagulation must be assessed individually . Good supportive care is essential. Immunoglobulin and corticosteroids are of limited value. Currently available antiviral compounds are not effective.

51. Treatment (cont.) the American Academy of Pediatrics recommends consideration of vitamin A supplementation for: children 6 mo to 2 yr of age who are hospitalized for measles and its complications children older than 6 mo of age with measles and immunodeficiency ;

52. Treatment (cont.) The recommended regimen is a single dose of: 100,000 IU orally for children 6 mo to 1 yr 200,000 IU for children 1 yr of age or older Children with ophthalmologic evidence of vitamin A deficiency should be given additional doses the next day and 4 wk later .

53. Complications The chief complications of measles are: otitis media pneumonia encephalitis .

54. Respiratory tract complications Interstitial pneumonia may be caused by the measles virus ( giant cell pneumonia ). Bacterial superinfection and bronchopneumonia are more frequent, however, usually with pneumococcus , group A Streptococcus , Staphylococcus aureus , and Haemophilus influenzae type b . Laryngitis , tracheitis , and bronchitis are common and may be due to the virus alone

55. Respiratory tract complications (cont.) Measles may exacerbate underlying Mycobacterium tuberculosis infection There may also be a temporary loss of hypersensitivity reaction to tuberculin skin testing. Measles pneumonia in HIV-infected patients is often fatal and is not always accompanied by rash

56. Cardiovascular complications Noma of the cheeks may occur in rare instances Gangrene elsewhere appears to be secondary to : purpura fulminans disseminated intravascular coagulation following measles Myocarditis is an infrequent serious complication, although transient electrocardiographic changes may be relatively common .

57. Neurologic complications Are more common in measles than in any of the other exanthematous diseases. Encephalomyelitis The i ncidence is estimated to be 1-2/1,000 cases of measles. There is no correlation between the severity of the : * Rash illness and that of the neurologic involvement * Initial encephalitic process and the prognosis.

58. Neurologic complications (cont.) Infrequently , encephalitic involvement is manifest in the pre-eruptive period , but more often its onset occurs 2-5 days after the appearance of the rash . The cause of measles encephalitis remains controversial . 1. Encephalitis early in the course of the disease : direct viral invasion may be operative for 2. Encephalitis that occurs later is predominantly demyelinating and may reflect an immunologic reaction . Fatal encephalitis has occurred in children receiving immunosuppressive treatment.

59. Neurologic complications (cont.) Other central nervous system complications, including: Guillain-Barré syndrome Hemiplegia Cerebral thrombophlebitis Retrobulbar neuritis occur rarely .

60. Prognosis Case fatality rates in the United States have decreased in recent years to low levels for all age groups, largely because of : Improved socioeconomic conditions Effective antibacterial therapy for the treatment of secondary bacterial infections. Despite the decline in measles cases and fatalities in the United States, the case fatality rate is still 1-3/1,000 cases .

61. Prognosis (cont.) Deaths are primarily due to pneumonia or secondary bacterial infections . In developing countries measles frequently occurs in infants ; possibly because of concomitant malnutrition, the disease is very severe in these locations and has a high mortality . When measles is introduced into a highly susceptible population , the results may be disastrous .

62. Prevention. Isolation precautions , especially in hospitals and other institutions, should be maintained from the 7th day after exposure until 5 days after the rash has appeared.

63. VACCINE The initial measles immunization, usually as measles-mumps-rubella ( MMR ) vaccine , is recommended at 12-15 mo of age MMR vaccine may be given for: 1. Measles postexposure 2. Outbreak prophylaxis as early as 6 mo of age .

64. VACCINE (cont.) A second immunization , also as MMR, is recommended routinely at 4-6 yr of age MMR may be administered at any time during childhood provided at least 4 wk have elapsed since the first dose . Second measles immunization should be given to : 1. Children who have not previously received the second dose should be immunized by 11-12 yr of age . 2.Adolescents entering college or the workforce

65. VACCINE (cont.) A tuberculin test prior to or concurrent with active immunization against measles is desirable if tuberculosis is under consideration.

66. VACCINE (cont.) * Measles vaccine is not recommended for: 1. Pregnant women 2. Children with primary immunodeficiency 3. Untreated tuberculosis, cancer, or organ transplantation 4. Those receiving long-term immunosuppressive therapy 5. severely immunocompromised HIV-infected children

67. VACCINE (cont.) HIV-infected children without : 1. Severe immunosuppression 2. Evidence of measles immunity may receive measles vaccine .

68. POSTEXPOSURE PROPHYLAXIS Passive immunization with immune globulin is effective for prevention and attenuation of measles within 6 days of exposure . Susceptible household and hospital contacts who are: 1. younger than 12 mo of age 2. pregnant should receive immune globulin ( 0.25 mL/kg ; maximum: 15 mL) intramuscularly as soon as possible after exposure, but within 5 days .

69. POSTEXPOSURE PROPHYLAXIS (cont.) Immunocompromised persons should receive immune globulin ( 0.5 mL/kg; maximum: 15 mL) intramuscularly regardless of immunization status. Infants 6 mo of age or younger born to nonimmune mothers should receive immune globulin ; infants 6 mo of age or younger born to immune mothers are considered protected by maternal antibody .

70. POSTEXPOSURE PROPHYLAXIS (cont.) Susceptible children 6-12 mo of age should also be vaccinated ; this vaccination does not count as one of the two required measles vaccinations. Susceptible children 12 mo of age or older should receive vaccine alone within 72 hr . Pregnant women and immunocompromised persons should receive immune globulin but not vaccine

71. References Centers for Disease Control and Prevention. : Epidemiology of measles – United States, 2001–2003. MMWR 2004; 53:713-716 Progress towards measles elimination, western hemisphere, 2002–2003 : Wkly Epidemiol Rec. 2004; 79:149-151 Yeung LF, Lurie P, Dayan G, et al: A limited measles outbreak in a highly vaccinated US boarding school. Pediatrics 2005; 116:1287. Parker AA, Staggs W, Dayan GH, et al: Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States. N Engl J Med 2006; 355:447-455 Centers for Disease Control and Prevention. : Licensure of a combined live attenuated measles, mumps, rubella, and varicella vaccine. MMWR 2005; 54:1212-1214 Bellini WJ, Rota JS, Lowe LE, et al: Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis 2005; 192:1686-1693.